Over the past 10 years, optical coherence tomography (OCT) has undergone a rapid development from inception to a versatile method for non-invasive high-resolution optical imaging. A wide range of medical diagnostic applications has been explored in ophthalmology, cardiology and in early cancer diagnosis in general. Preliminary studies have demonstrated that OCT can facilitate the accurate diagnosis of a variety of diseases when used in a point-sampling protocol analogous to random biopsy. The potential diagnostic applications having the highest impact, however, require screening or surveillance of large tissue volumes. The relatively slow image acquisition rate of current OCT technology therefore represents a significant barrier to its utility as a powerful clinical tool. Since the current technology commonly operates at its theoretical limit for efficient light collection, dramatic improvements in imaging speed can only be obtained through a technological paradigm shift. We propose to develop a new, parallel detection principle for OCT that is several hundred-fold more efficient than current state of the art technology and that provides vastly improved image acquisition rate and resolution. The system design of the proposed technology is tailored to three high-impact clinical goals: early detection and monitoring of glaucoma, the second-leading cause of blindness in the U.S, detection and characterization of vulnerable coronary plaques responsible for acute myocardial infarction, and comprehensive surveillance for esophageal neoplasia in patients with Barrett's esophagus. Three clinical pilot studies, using technology developed in this work, will be conducted to test system performance relevant to achieving these goals.